The Role and the Molecular Mechanisms of Homeostatic Inflammation in the Pathophysiology of Cardiac Hypertrophy

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860586
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: HIGASHIKUNI YASUTOMI 東京大学, 医学部附属病院, 助教 (10586481)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 自然炎症 / 心肥大 / 心不全 / TLR2 / 熱ショック蛋白質 / IL-1β / NLRP3 / インフラマソーム

Outline of Final Research Achievements

To investigate the role of homeostatic inflammation in cardiac hypertrophy, we assessed the role of pattern recognition receptors in the pathophysiology of pressure overload-induced cardiac hypertrophy. We clarified that Toll-like receptor 2-mediated interleukin 1β production, induced by extracellularly released heat shock protein 70, is essential for adaptive cardiac hypertrophy in response to pressure overload. In addition, we found that the NLRP3 inflammasome, a multiprotein complex involved in the innate immune response, regulates active IL-1β production in the heart during pressure overload and contribute to adaptive cardiac hypertrophy. These results revealed the essential role and the underlying mechanisms of homeostatic inflammation in the pathophysiology of pressure overload-induced cardiac hypertrophy.

Free Research Field

医歯薬学